Coenzyme pyruvate

IS the oxidation of lactic acid to pyruvic acid by NAD and the enzyme lactic acid coenzyme NAD ... 

The enzyme is a single enantiomer of a chiral molecule and binds the coenzyme and substrate m such a way that hydride is transferred exclusively to the face of the carbonyl group that leads to (5) (+) lactic acid Reduction of pyruvic acid m the absence of an enzyme however say with sodium borohydride also gives lactic acid but as a racemic mixture containing equal quantities of the R and S enantiomers... 

The form in which acetate is used in most of its important biochemical reactions is acetyl coenzyme A (Figure 26 la) Acetyl coenzyme A is a thwester (Section 20 13) Its for matron from pyruvate involves several steps and is summarized m the overall equation... 

Krebs Cycle The oxidative process in respiration by which pyruvate (via acetyl coenzyme A) is completely decarboxylated to COj. The pathway yields 15 moles of ATP (150,000 calories). 

The pyruvate dehydrogenase complex (PDC) is a noncovalent assembly of three different enzymes operating in concert to catalyze successive steps in the conversion of pyruvate to acetyl-CoA. The active sites of ail three enzymes are not far removed from one another, and the product of the first enzyme is passed directly to the second enzyme and so on, without diffusion of substrates and products through the solution. The overall reaction (see A Deeper Look Reaction Mechanism of the Pyruvate Dehydrogenase Complex ) involves a total of five coenzymes thiamine pyrophosphate, coenzyme A, lipoic acid, NAD+, and FAD. 

The mechanism of the pyruvate dehydrogenase reaction is a tour de force of mechanistic chemistry, involving as it does a total of three enzymes (a) and five different coenzymes—thiamine pyrophosphate, lipoic acid, coenzyme A, FAD, and NAD (b). 

Two particularly interesting aspects of the pyruvate carboxylase reaction are (a) allosteric activation of the enzyme by acyl-coenzyme A derivatives and (b) compartmentation of the reaction in the mitochondrial matrix. The carboxy-lation of biotin requires the presence (at an allosteric site) of acetyl-coenzyme A or other acylated coenzyme A derivatives. The second half of the carboxylase reaction—the attack by pyruvate to form oxaloacetate—is not affected by CoA derivatives. 

Carboxylic acids with labile a-methylene protons react with isatin in the presence of strong aqueous base. In the total synthesis of methoxatin, the coenzyme of methanol dehydrogenase and glucose dehydrogenase, Weinreb employs a Pfitzinger condensation of an isatin 37 and pyruvic acid as a key step to provide the 4-quinolinic acid 38 in 50% yield under the standard basic conditions. ... 

Figure 29.11 MECHANISM Mechanism of the conversion of pyruvate to acetyl CoA through a multistep sequence of reactions that requires three different enzymes and four different coenzymes. The individual steps are explained in the text.

Step 4 of Figure 29.12 Oxidative Decarboxylation The transformation of cr-ketoglutarate to succinyl CoA in step 4 is a multistep process just like the transformation of pyruvate to acetyl CoA that we saw in Figure 29.11. In both cases, an -keto acid loses C02 and is oxidized to a thioester in a series of steps catalyzed by a multienzynie dehydrogenase complex. As in the conversion of pyruvate to acetyl CoA, the reaction involves an initial nucleophilic addition reaction to a-ketoglutarate by thiamin diphosphate vlide, followed by decarboxylation, reaction with lipoamide, elimination of TPP vlide, and finally a transesterification of the dihydrolipoamide thioester with coenzyme A. 

Step 1 of Figure 29.13 Carboxylation Gluconeogenesis begins with the carboxyl-afion of pyruvate to yield oxaloacetate. The reaction is catalyzed by pyruvate carboxylase and requires ATP, bicarbonate ion, and the coenzyme biotin, which acts as a carrier to transport CO2 to the enzyme active site. The mechanism is analogous to that of step 3 in fatty-acid biosynthesis (Figure 29.6), in which acetyl CoA is carboxylated to yield malonyl CoA. 

Lactate, a product of glucose catabolism in oxygen-starved muscles, can be converted into pyruvate by oxidation. What coenzyme do you think is needed Write the equation in the normal biochemical format using a curved arrow. 

Several enzymes of the intermediary metabolism require thiaminpyrophosphate (TPP, Fig. 1) as coenzyme, e.g., enzymes of the pyruvate dehydrogenase complex, a-ketoglutarate dehydrogenase complex, or pentose phosphate pathway. 

Mitochondrial pyruvate carboxylase catalyzes the cat-boxylation of pymvate to oxaloacetate, an ATP-tequit-ing reaction in which the vitamin biotin is the coenzyme. Biotin binds CO2 from bicatbonate as carboxybiotin ptiot to the addition of the COj to pym-... 

B, Thiamin Coenzyme in pyruvate and a-ketoglutarate, dehydrogenases, and transketolase poorly defined function in nerve conduction Peripheral nerve damage (beriberi) or central nervous system lesions (Wernicke-Korsakoff syndrome)... 

Since, in order to decarboxylate pyruvate, the cofactor (6-thioctic acid) must be in its oxidized form, Calvin suggested that, in the presence of light, the coenzyme shifts to the reduced (dithiol) form, thus markedly reducing the rate of incorporation of C14 into the Krebs cycle. Furthermore, Bradley and Calvin236(f) suggested that 6-thioctic acid is an acceptor of... 

Abnormalities of the respiratoiy chain. These are increasingly identified as the hallmark of mitochondrial diseases or mitochondrial encephalomyopathies [13]. They can be identified on the basis of polarographic studies showing differential impairment in the ability of isolated intact mitochondria to use different substrates. For example, defective respiration with NAD-dependent substrates, such as pyruvate and malate, but normal respiration with FAD-dependent substrates, such as succinate, suggests an isolated defect of complex I (Fig. 42-3). However, defective respiration with both types of substrates in the presence of normal cytochrome c oxidase activity, also termed complex IV, localizes the lesions to complex III (Fig. 42-3). Because frozen muscle is much more commonly available than fresh tissue, electron transport is usually measured through discrete portions of the respiratory chain. Thus, isolated defects of NADH-cytochrome c reductase, or NADH-coenzyme Q (CoQ) reductase suggest a problem within complex I, while a simultaneous defect of NADH and succinate-cytochrome c reductase activities points to a biochemical error in complex III (Fig. 42-3). Isolated defects of complex III can be confirmed by measuring reduced CoQ-cytochrome c reductase activity. 

The clinical significance of thiamine and its necessity for pyruvic acid oxidation has been discussed. Recent reports concerning the coenzyme function of thiamine in pentose (H13), tryptophan (D2), and lipoic acid metabolism (R6) have increased our knowledge of thiamine in metabolism and lend added interest to the role of thiamine in clinical problems. This method has also been used to assay thiamine in liver and brain. 

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